Instructions Jive solution for injection (ampoule A) in ampoules of 2 ml 5 pcs + solvent (ampoule B) of 1 ml No. 5
Composition
active ingredients: glucosamine, sodium chloride;
1 ml of solution for injection (ampoule A) contains 251.25 mg of glucosamine sulfate sodium chloride, which is equivalent to glucosamine sulfate 200 mg and sodium chloride 51.25 mg;
excipients:
ampoule A: lidocaine hydrochloride, diluted or concentrated hydrochloric acid, water for injection;
ampoule B (solvent): diethanolamine, water for injection.
Dosage form
Solution for injection.
Main physicochemical properties:
ampoule A – transparent colorless or light yellow-brown solution;
ampoule B (solvent) – a clear colorless solution;
ampoule A+B (solution for injection) – a clear colorless or light yellow-brown solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Other nonsteroidal anti-inflammatory and antirheumatic drugs. Glucosamine. ATX code M01A X05.
Pharmacological properties
Pharmacodynamics
The active ingredient, glucosamine sulfate, is a salt of the aminomonosaccharide glucosamine, which is present in the human body under physiological conditions and is used together with sulfates for the biosynthesis of hyaluronic acid in the synovial fluid and glycosaminoglycans in the ground substance of articular cartilage.
Thus, the mechanism of action of glucosamine sulfate is to stimulate the synthesis of glycosaminoglycans and, accordingly, articular proteoglycans. In addition, glucosamine has an anti-inflammatory effect and inhibits the process of destruction of articular cartilage, mainly due to the possible manifestations of its own metabolic properties, the ability to inhibit the activity of interleukin 1 (IL-1), which, on the one hand, affects the symptoms of osteoarthritis, and on the other hand, potentially delays structural damage to the joints, as evidenced by data from long-term clinical studies.
According to initial in vitro and in vivo studies, exogenous administration of glucosamine sulfate stimulates proteoglycan biosynthesis, which is deficient in osteoarthritis, promotes the fixation of sulfur ions during the synthesis of glycosaminoglycans, and improves trophicity of articular cartilage.
Further studies have shown that glucosamine sulfate inhibits the synthesis of tissue-degrading substances such as superoxide radicals, as well as the activity of lysosomal enzymes in addition to enzymes capable of destroying articular cartilage tissue, such as collagenases and phospholipase A2. Glucosamine sulfate also has a moderate anti-inflammatory effect, which is observed in in vivo animal models, including in some cases in experimental osteoarthritis, even without inhibition of cyclooxygenases, unlike nonsteroidal anti-inflammatory drugs (NSAIDs).
More recent studies have shown that most of the above metabolic and anti-inflammatory effects may be related to the inhibition of intracellular signal transduction of IL-1, one of the cytokines involved in the pathogenesis of osteoarthritis, with subsequent inhibition of cytokine-induced gene transcription. Glucosamine sulfate, at plasma and synovial fluid concentrations reported in patients with osteoarthritis, can actually inhibit IL-1-induced gene expression of a series of pro-inflammatory enzymes in joint tissues, as well as pro-degenerative enzymes in cartilage, such as some metalloproteases, including aggrecanases. The potential influence of sulfur ions on the aforementioned pharmacodynamic properties of glucosamine is not fully understood.
All of the above properties have a beneficial effect on the degenerative processes in cartilage that underlie the pathogenesis of osteoarthritis, as well as on the clinical picture of the disease.
Short-term and medium-term studies have shown that the effectiveness of glucosamine sulfate on osteoarthritis symptoms is evident as early as 2–3 weeks after starting its use.
On the other hand, the efficacy of glucosamine sulfate treatment on symptoms, compared with conventional analgesics and nonsteroidal anti-inflammatory drugs, is optimal after a course of continuous use for 6 months or after a course of use for 3 months with an obvious aftereffect for 2 months after discontinuation.
Clinical trial results of daily continuous treatment over 3 years show a progressive increase in its effectiveness, with regard to symptoms and slowing of structural joint damage, as confirmed by X-ray.
Glucosamine sulfate has been shown to be well tolerated. No significant effects of glucosamine sulfate on the cardiovascular, respiratory, autonomic, or central nervous systems have been identified.
Studies in humans and animals have shown that after oral administration of 14C-glucosamine, the radiolabeled elements are rapidly and almost completely absorbed systemically. In humans, about 90% of the radiolabeled dose is absorbed. The absolute bioavailability of glucosamine in rats after oral administration of glucosamine sulfate was 26% due to the first-pass effect. The absolute bioavailability in humans is unknown, but allometric calculations suggest that it is similar to that observed in rats, i.e. 20 to 30%.
In healthy volunteers, after multiple oral doses of glucosamine sulfate at a dose of 1500 mg per day, the maximum steady-state plasma concentration (Cmax,ss) was 1602 ± 425 ng/ml (8.9 µM). This concentration was reached 1.5–4 hours (median 3 hours) after administration (tmax). At steady state, the AUC of plasma concentrations versus time was 14564 ± 4138 ng h/ml. These parameters were obtained when the drug was administered in the fasting state, so it is unknown whether food intake can significantly affect the absorption of the drug.
After oral administration, glucosamine is mainly distributed in the extravascular environment (including synovial fluid) after absorption, with a volume of distribution approximately 37 times greater than the total amount of water in the human body. Glucosamine is not protein bound.
The metabolic profile of glucosamine was not investigated because this drug, which is a natural substance present in the human body, is used for the biosynthesis of some components of articular cartilage.
Only the terminal elimination half-life of glucosamine from human plasma has been determined from a study of plasma glucosamine levels measured for 48 hours after oral administration of the drug. The calculated value was approximately 15 hours.
Following oral administration of 14C-glucosamine, urinary excretion of radiolabeled elements in humans was 10 ± 9% of the administered dose, while faecal excretion was 11.3 ± 0.1%. Urinary excretion of unchanged glucosamine in humans following oral administration was on average low (approximately 1% of the administered dose). These results indicate that the kidneys do not play a significant role in the elimination of glucosamine and/or its metabolites and/or breakdown products.
Glucosamine pharmacokinetics were linear after multiple dosing of 750–1500 mg once daily, whereas plasma glucosamine levels were lower than expected with increasing doses at 3000 mg. Steady-state glucosamine pharmacokinetics were not time-dependent, and showed no evidence of accumulation or reduced bioavailability compared to the pharmacokinetic profile observed after single administration.
The pharmacokinetics of glucosamine in men and women are similar, and no differences in pharmacokinetics have been found between healthy volunteers and patients with osteoarthritis of the knee. In the latter, the mean plasma concentration 3 hours after the last dose of 1500 mg with repeated administration once daily was 7.2 µM and was similar to that found in healthy volunteers, while the mean concentration in synovial fluid was only 25% lower and therefore also in the 10 µM range. The pharmacokinetics of glucosamine have not been studied in patients with renal or hepatic insufficiency, since, given the safety profile of the drug and due to the minor involvement of the kidneys in the elimination of glucosamine, no dose reduction is envisaged for these patient groups.
The equilibrium concentrations of glucosamine in blood plasma and synovial fluid after repeated administration of 1500 mg once daily are within 10 mM and, therefore, correspond to those for which pharmacological activity has been shown in studies in in vitro experimental models, which confirms the mechanism of action and clinical effect of the drug.
Indication
Relief of symptoms in mild to moderate osteoarthritis of the knee.
Contraindication
Individual hypersensitivity to the active substance or to any of the excipients, tendency to bleeding.
Jive should not be used in patients with shellfish allergies, as the active ingredient is derived from shellfish shells; such patients may be more likely to develop allergic reactions to glucosamine with possible exacerbation of symptoms.
The medicinal product contains the excipient lidocaine, which has the following contraindications: cardiogenic shock; severe arterial hypotension; acute heart failure; severe forms of chronic heart failure; reduced left ventricular function; heart conduction disease; atrioventricular block of the II-III degree; severe bradycardia; blood clotting disorders; Wolff-Parkinson-White syndrome; Adams-Stokes syndrome; history of seizures caused by the use of lidocaine; sick sinus syndrome; severe liver dysfunction; hypovolemia; myasthenia gravis; infections at the injection site; hypersensitivity to lidocaine and hypersensitivity to other amide-type anesthetics (since there is an increased risk of developing cross-hypersensitivity reactions).
Interaction with other medicinal products and other types of interactions
Mixing the contents of ampoules of the medicinal product with other injectable drugs should be avoided.
Specific drug interaction studies have not been performed. However, given the physicochemical and pharmacokinetic properties of glucosamine sulfate, the potential for interactions is expected to be low. In addition, glucosamine sulfate has been shown to neither inhibit nor induce the major human CYP450 enzymes.
In fact, the drug does not compete for absorption mechanisms; after absorption, it does not bind to blood plasma proteins, but is metabolized by incorporation as an endogenous substance into proteoglycans or is broken down without the participation of enzymes of the cytochrome system, as a result of which its interaction with other drugs is unlikely.
There is limited data on possible drug interactions with glucosamine, however, increases in INR (international normalized ratio) have been observed with oral vitamin K antagonists. Therefore, patients receiving oral vitamin K antagonists should be closely monitored when initiating or discontinuing glucosamine therapy. Concomitant treatment with glucosamine may increase the absorption and, consequently, the serum concentration of tetracyclines. However, the clinical significance of this interaction is likely to be limited.
The drug is compatible with NSAIDs and glucocorticosteroids.
The drug contains the excipient lidocaine. Cimetidine, peptidine, bupivacaine, propranolol, quinidine, disopyramide, amitriptyline, nortriptyline, chlorpromazine, imipramine increase the level of lidocaine in the blood serum, reducing its hepatic metabolism. Noradrenaline exhibits a synergistic effect when interacting with lidocaine.
Monoamine oxidase inhibitors (MAOIs) should be used with caution, as they increase the risk of developing arterial hypotension and prolong the local anesthetic effect of the latter.
When used simultaneously with class IA antiarrhythmic drugs (including quinidine, procainamide, disopyramide), the QT interval is prolonged, and in very rare cases, AV block or ventricular fibrillation may develop.
The cardiotonic effect of cardiac glycosides is weakened.
When used simultaneously with sedatives, the sedative effects are enhanced.
Phenytoin enhances the cardiodepressive effect of lidocaine.
When used simultaneously with procainamide, delusions and hallucinations are possible.
Lidocaine may enhance the effect of drugs that cause neuromuscular blockade, since the latter reduce the conductivity of nerve impulses. Ethanol enhances the respiratory depressant effect of lidocaine.
Application features
The drug can only be administered by medical professionals.
In patients with a known risk factor for cardiovascular disease, monitoring of blood lipid levels is recommended, as hypercholesterolemia has been observed in several cases in patients receiving glucosamine.
It should be prescribed with caution to patients with glucose intolerance. At the beginning of treatment, it is advisable to monitor blood sugar levels in patients with diabetes.
There have been cases of exacerbation of asthma symptoms after starting glucosamine (symptoms of exacerbation disappeared after discontinuation of glucosamine). Therefore, the drug should be used with caution in the treatment of patients suffering from bronchial asthma, since such patients may be more prone to developing allergic reactions to glucosamine with possible exacerbation of symptoms of the disease. Special studies in patients with renal or hepatic insufficiency have not been conducted. However, the use of glucosamine in patients with severe hepatic or renal insufficiency should be monitored.
One dose of the medicinal product contains 40.3 mg of sodium. This should be taken into account when prescribing to patients on a strict salt-free diet.
To avoid accidental intravasal administration of the drug, it is recommended to perform an aspiration test.
The safety of lidocaine-type anesthetics is questionable in patients prone to malignant hyperthermia, so their use should be avoided.
Before using lidocaine for heart diseases (hypokalemia reduces the effectiveness of lidocaine), it is necessary to normalize the level of potassium in the blood and monitor the ECG.
Serum creatine phosphokinase activity may increase after intramuscular injection of the drug, which may lead to an error in the diagnosis of acute myocardial infarction.
In case of sinus node dysfunction, prolongation of the P-Q interval, QRS widening, or in case of the occurrence or exacerbation of arrhythmia, the dose should be reduced or the drug should be discontinued.
Special caution should be exercised when administering the drug to patients with circulatory failure, arterial hypotension, a history of arrhythmias, moderate hepatic and/or renal dysfunction. Given the presence of lidocaine in the composition, caution should also be exercised when prescribing the drug to elderly patients, patients with epilepsy, with impaired cardiac conduction, and with respiratory failure.
Use during pregnancy or breastfeeding
There is no data on the use of the drug in pregnant or breastfeeding women, therefore the use of the drug in this category of patients is contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of the drug on the ability to drive and use other mechanisms have not been conducted. Dizziness, drowsiness, fatigue, cephalalgia or visual disturbances may develop during the use of glucosamine, so driving and operating other mechanisms should be avoided.
Method of administration and doses
For intramuscular use!
The drug is not intended for intravenous administration.
Adult and elderly patients
Before use, mix solution B (solvent 1 ml) with solution A (drug solution 2 ml) in one syringe.
The prepared solution for injection (solution A+B) should be administered intramuscularly in 3 ml or 6 ml 3 times a week for 4–6 weeks.
The presence of a yellowish color of the solution in ampoule A does not affect the efficacy and tolerability of the medicinal product.
The drug can be combined with oral forms of glucosamine.
Glucosamine is not indicated for the treatment of acute pain.
Relief of symptoms (especially pain relief) is possible only after several weeks of treatment, and in some cases even after a longer period of time.
If no relief of symptoms occurs after 2–3 months of use, treatment should be reviewed.
Use in elderly patients
No studies on the kinetics of glucosamine have been conducted in elderly patients.
Use in patients with renal and/or hepatic insufficiency
No studies on the kinetics of glucosamine have been conducted in this population (see section "Special warnings and precautions for use").
Children.
Do not use in children and adolescents, as the safety and effectiveness of glucosamine in such patients have not been established.
Overdose
No cases of overdose (accidental or intentional) have been reported. In case of overdose, the drug should be discontinued and, if necessary, symptomatic treatment should be carried out to restore water and electrolyte balance.
The drug contains the excipient lidocaine. The first symptoms of an overdose of lidocaine hydrochloride from the central nervous system may be numbness of the tongue and lips, excitement, euphoria, anxiety, tinnitus, dizziness, blurred vision, nystagmus, tremor, depression, drowsiness, loss of consciousness, up to coma, tonic-clonic convulsions. As is known from publications, symptoms of an overdose associated with lidocaine hydrochloride from the cardiovascular system and respiratory function may be a decrease in blood pressure, collapse, AV block and respiratory depression. It is necessary to monitor the patient's cardiovascular and respiratory function. A change in these parameters may indicate an overdose of the drug, so the patient should immediately be provided with oxygen access. All complications require symptomatic treatment.
Adverse reactions
Criteria for assessing the frequency of adverse drug reactions: very common (> 1/10), common (> 1/100 to 1/10), uncommon (> 1/1000 to 1/100), rare (> 1/10000 to 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from the available information).
On the part of the immune system: frequency unknown - allergic reactions (hypersensitivity).
Metabolism and nutrition disorders: frequency unknown - negative effect on blood sugar monitoring, hyperglycemia in patients with impaired glucose tolerance.
On the part of the psyche: frequency unknown - insomnia.
From the nervous system: often - cephalalgia (headache), drowsiness; frequency unknown - dizziness.
On the part of the organs of vision: frequency unknown - visual impairment.
Cardiac disorders: frequency unknown - cardiac arrhythmia, e.g. tachycardia.
Vascular disorders: infrequently - redness.
Gastrointestinal: often - nausea, abdominal pain, indigestion, diarrhea, constipation, flatulence, heaviness in the stomach and pain, dyspepsia.
Skin and subcutaneous tissue disorders: uncommon – erythema, rash, itching; frequency unknown – hair loss, angioedema, urticaria.
Respiratory, thoracic and mediastinal disorders: frequency unknown - asthma, exacerbation of asthma.
Hepatobiliary system: frequency unknown - jaundice.
General disorders and administration site conditions: common: fatigue; frequency unknown: edema, peripheral edema, injection site reaction.
Investigations: frequency unknown – increased liver enzymes, increased blood glucose levels, increased blood pressure, INR fluctuations.
Isolated cases of spontaneous hypercholesterolemia have been reported, but a causal relationship has not been established.
The medicine contains lidocaine. In exceptional cases, the following side effects are possible, which are characteristic of this component.
Nervous system: numbness of the tongue and lips, photophobia, diplopia, headache, confusion, muscle twitching, when used in high doses - tinnitus, excited state, anxiety, paresthesia, convulsions, loss of consciousness, coma, hyperacusis.
On the part of the organs of vision: visual impairment, conjunctivitis, when used in high doses - nystagmus.
On the part of the psyche: frequency unknown - sleep disorders.
From the cardiovascular system: arterial hypotension, transverse heart block; frequency unknown - increased blood pressure, when used in high doses - arrhythmia, bradycardia, slowing of cardiac conduction, cardiac arrest, peripheral vasodilation, collapse, tachycardia, pain in the heart area.
Immune system disorders: immune system suppression, allergic reactions, including edema, skin reactions, itching; very rarely - urticaria, hypersensitivity reactions, including anaphylactoid reactions (including anaphylactic shock), generalized exfoliative dermatitis.
Respiratory, thoracic and mediastinal disorders: respiratory depression or respiratory arrest, shortness of breath.
Other: feeling of heat, cold or numbness of the extremities, malignant hyperthermia, when used in high doses - rhinitis.
General disorders and administration site conditions: tingling of the skin at the injection site, abscess, mild burning sensation (disappears with the development of the anesthetic effect within 1 minute), thrombophlebitis.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
2 ml in ampoules, 5 ampoules (ampoule A) in a blister complete with solvent 1 ml in ampoules, 5 ampoules (ampoule B) in a blister in a cardboard pack.
Vacation category
According to the recipe.
Producer
LLC NVF "MICROCHEM".
Address
Ukraine, 93400, Luhansk region, Severodonetsk city, Promyslova st., building 24-v.
